Biomedical subjects

B E Levin

Publications and source records attributed to B E Levin.

At least 55 records · Page 3Linked to original sources

PubMed1997

Low-affinity sulfonylurea binding sites reside on neuronal cell bodies in the brain.

The antidiabetic sulfonylurea drugs bind to sites associated with an ATP-sensitive potassium (Katp) channel on cell bodies and terminals of neurons which increase their firing rates or transmitter release when glucose concentrations rise or sulfonylureas are present. High-affinity sulfonylurea binding sites are concentrated in areas such as the substantia nigra (SN) where glucose and sulfonylureas increase transmitter release from GABA neurons. But there is a paucity of high-affinity sites in areas such as the hypothalamic ventromedial nucleus (VMN) where many neurons increase their activity when glucose rises. Here we assessed both high- and low--affinity sulfonylurea binding autoradiographically with 20 nM [3H]glyburide in the presence of absence of Gpp(NH)p. Neurotoxin lesions with 6-hydroxydopamine (6-OHDA), 5,7-dihydroxytryptamine (5,7-DHT) and ibotenic acid were used to elucidate the cellular location of the two sites in the VMN, SN and locus coeruleus (LC). In the VMN, 25% of the sites were of low affinity. Neither 6-OHDA nor 5,7-DHT affected [3H]glyburide binding, while ibotenic acid reduced the number of VMN neurons and abolished low-affinity without changing high-affinity binding. In cell-attached patches of isolated VMN neurons, both 10 mM glucose and 100 microM glyburide decreased the open probability of the Katp channel suggesting that the low-affinity binding site resides on these neurons. In the SN pars reticulata, ibotenic acid reduced the number of neurons and high-affinity [3H]glyburide binding was decreased by 20%, while 6-OHDA had no effect. In the SN pars compacta, both 6-OHDA and ibotenic acid destroyed endogenous dopamine neurons and selectivity ablated low-affinity binding. In the LC, 6-OHDA destroyed norepinephrine neurons and abolished low-affinity binding. These data suggest that low-affinity sulfonylurea binding sites reside on cell bodies on VMN, SN dopamine and LC norepinephrine neuron cell bodies and that high-affinity sites may be on axon terminals of GABA neurons in the SN.

5,7-Dihydroxytryptamine↗

PubMed1997

Location and effect of obesity on putative anorectic binding sites in the rat brain.

Anorectic drugs such as mazindol bind to a class of low-affinity, sodium-sensitive sites in the brain which are affected by ambient glucose concentrations and a predisposition to develop diet-induced obesity (DIO). This study used quantitative autoradiography of 10 nM 3H-mazindol binding to identify the cellular location of these putative anorectic binding sites in the brain and to assess the way in which the development of DIO affected their binding. We previously showed that chow-fed, obesity-prone rats have widespread increases in brain 3H-mazindol binding to these low-affinity sites as compared with diet-resistant (DR) rats. Here, low-affinity 3H-mazindol binding was assessed in the brains of eight rats which developed DIO vs. eight which were DR after three months on a high-energy diet. DIO rats gained 89% more weight and had 117% higher plasma insulin levels but no difference in plasma glucose levels compared with DR rats. Along with these differences, low-affinity 3H-mazindol binding in DIO rats was identical to that in DR rats in all of the 23 brain areas assessed. This suggested that this binding was downregulated by the development of obesity in DIO rats. In other chow-fed rats, stereotaxic injections of 5,7-dihydroxytryptamine and 6-hydroxydopamine (6OHDA) to ablate serotonin and catecholamine nerve terminals in the ventromedial nucleus of the hypothalamus (VMN) had no effect on 3H-mazindol binding. However, ibotenic acid injected into the VMN, substantia nigra, pars reticulata, and pars compacta destroyed intrinsic neurons and/or their local processes and decreased low-affinity 3H-mazindol binding by 13%-22%. Destruction of dopamine neurons in the substantia nigra, pars compacta, and noradrenergic neurons in the locus ceruleus with 6OHDA also reduced 3H-mazindol binding in those areas by 9% and 12%, respectively. This suggested that up to 22% of putative anorectic binding sites may be located on the cell bodies of dopamine, norepinephrine, and other neurons, but not on serotonin or catecholamine nerve terminals in the brain. Binding to these sites may be downregulated by the development of DIO, possibly as a result of the concomitant hyperinsulinemia.

Animals↗

PubMed1997

Alpha 1-adrenoceptor blockade increases behavioral deficits in traumatic brain injury.

Experimental enhancement of noradrenergic activity following traumatic brain injury (TBI) accelerates behavioral recovery if performed at a time when brain norepinephrine (NE) turnover is decreased. But, since NE turnover is markedely increased immediately after TBI, the present study was undertaken to evaluate the effect of modulating these early changes in NE metabolism on recovery of function. Rats were pretrained on a modified beam walking task. Thirty minutes prior to unilateral somatosensory cortex contusion they were treated with a NE reuptake blocker [desmethy-limipramine (DMI); 10 mg/kg, ip, n = 6] or an alpha 1-adrenoreceptor antagonist [prazosin (PRZ); 3 mg/kg, ip, n = 6]. PRZ pretreatment markedly worsened beam walking performance throughout the 3 weeks following injury, whilst DMI pretreatment did not affect performance compared to injured controls (n = 4). Despite the marked behavioral deficits, PRZ-treated animals showed no apparent worsening of histological damage (n = 11 per group) and lesion size was the same in all groups. In separate experiments (n = 4 per group), PRZ lowered basal blood pressure and prevented the rise in pressure immediately following TBI. However, blood pressures in the three groups came to the same level within 20 sec following TBI. This suggest that the action of PRZ was not simply due to hypotension-induced ischemia. It is possible that blockade of alpha 1-adrenoreceptors in the immediate posttrauma period leads to enhancement of excitatory neurotransmission, which exacerbates behavioral deficits.

Adrenergic Uptake Inhibitors↗

PubMed1997

Dysregulation of arcuate nucleus preproneuropeptide Y mRNA in diet-induced obese rats.

Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) produce metabolic and physiological effects that promote the development and maintenance of obesity. In turn, NPY metabolism in these neurons is inhibited by dopamine release. In this study, ARC prepro-NPY mRNA and ARC/median eminence (ME) dopamine turnover were assessed in chow-fed male Sprague-Dawley rats prone to develop diet-induced obesity (DIO) or to be diet resistant (DR) when fed a high-energy (HE) diet. By in situ hybridization, DIO-prone rats had 39% more ARC NPY mRNA expression than DR-prone rats under chow-fed conditions. DIO-prone rat ARC/ME dopamine levels were 14% higher, but dopamine half-life was 176% longer and turnover was 59% less than DR-prone rats. Neither a 48-h fast nor 50% energy intake restriction for 5 days affected the already increased ARC NPY mRNA levels in DIO-prone rats. Both manipulations increased NPY expression to the level of DIO-prone rats in DR-prone rats by 23 and 35%, respectively. Finally, when fed HE diet for 2 wk, neither DIO- nor DR-prone rats altered their ARC NPY expression despite the development of obesity and hyperinsulinemia in DIO rats. Thus DIO-prone rats overexpress and fail to regulate ARC NPY mRNA to energy restriction or hyperinsulinemia. This dysregulation is possibly secondary to reduced inhibition because of defective ARC/ME dopamine turnover. Both may be important predisposing factors in the development of DIO.

Animals↗

PubMed1997

Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats.

In outbred Sprague-Dawley rats, about one-half develop diet-induced obesity (DIO) on a diet relatively high in fat and energy (HE diet). The rest are diet resistant (DR), gaining weight and fat at the same rate as chow-fed controls. Here we selectively bred for high (DIO) and low (DR) weight gainers after 2 wk on HE diet. By the F5 generation, both male and female inbred DIO rats gained > 90% more weight than inbred DR rats on HE diets. Even on low-fat chow diet, DIO males were 31% and females were 22% heavier than their respective DR rats. Full metabolic characterization in male rats showed that weight-matched, chow-fed DIO-prone rats had similar energy intakes and feed efficiency [body weight (kg0.75)/energy intake (kcal)] but 44% more carcass fat than comparable DR-prone rats. Their basal plasma insulin and glucose levels in the fed state were 70 and 14% higher, respectively. But, when fasted, DIO-prone oral glucose tolerance results were comparable to DR-prone rats. Chow-fed DIO-prone males also had 42% greater 24-h urine norepinephrine levels than DR-prone males. During 2 wk on HE diet, DIO rats ate 25% more, gained 115% more weight, had 36% more carcass fat, and were 42% more feed efficient than comparable DR rats. Fasted HE diet-fed DIO rats developed frank glucose intolerance during a glucose tolerance test with 55 and 158% greater insulin and glucose areas under the curve, respectively. Thus the DIO and DR traits in the outbred Sprague-Dawley population appear to be due to a polygenic pattern of inheritance.

Animal Husbandry↗

PubMed1996

Differential effects of diet and obesity on high and low affinity sulfonylurea binding sites in the rat brain.

The brain contains neurons which alter their firing rates when ambient glucose concentrations change. An ATP-sensitive K+ (Katp) channel on these neurons closes and increases cell firing when ATP is produced by intracellular glucose metabolism. Binding of the antidiabetic sulfonylurea drugs to a site linked to this channel has a similar effect. Here rats with a propensity to develop diet-induced obesity (DIO) or to be diet-resistant (DR) when fed a diet moderately high in fat, energy and sucrose (HE diet) had low and high affinity sulfonylurea binding assessed autoradiographically with [3H]glyburide in the presence or absence of Gpp(NH)p. Before HE diet exposure, chow-fed DIO- and DR-prone rats were separated by their high vs. low 24 h urine NE levels. In DR-prone rats, low affinity [3H]glyburide binding sites comprised up to 45% of total binding with highest concentrations in the hypothalamus and amygdala. But DIO-prone rats had few or no low affinity binding sites throughout the forebrain. High affinity [3H]glyburide binding was similar between phenotypes. When rats developed DIO after 3 months on HE diet, their low affinity binding increased slightly. DR rats fed the HE diet gained the same amount of weight as chow-fed controls but their low affinity binding sites were reduced to DIO levels and both were significantly lower than chow-fed controls. By contrast, high affinity [3H]glyburide binding was increased in DR rats throughout the forebrain so that it significantly exceeded that in both DIO and chow-fed control rats. These studies demonstrate a significant population of low affinity sulfonylurea binding sites throughout the forebrain which, along with high affinity sites, are regulated as a function of both weight gain phenotype and diet composition.

ATP-Binding Cassette Transporters↗

PubMed1996

Reduced paraventricular nucleus norepinephrine responsiveness in obesity-prone rats.

Male Sprague-Dawley rats prone to develop diet-induced obesity (DIO-prone) when fed a high-energy diet have several deficits in brain noradrenergic function compared with diet-resistant (DR) rats. To further characterize these deficits, 3-mo-old rats were identified prospectively as being DIO- or DR-prone rats by their high (DIO-prone) or low (DR-prone) 24-h urine norepinephrine (NE) levels. Saturation-binding studies with 0.2-20 nM [3H] paraminoclonidine to alpha 2-adrenoceptors showed 27-54% decreases in maximal binding capacity in the anterior hypothalamic area, paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMN), and basolateral amygdalar nucleus of DIO- vs. DR-prone rats. The areal extent of the VMN was selectively reduced by 15% in DIO-prone rats. Freely moving, catheterized DIO-prone rats had higher basal plasma glucose (9%) and insulin (31%) levels. Bilateral 3 nmol NE infusions over 20 min into the PVN increased plasma NE (175%) and insulin (31%) levels in DR-prone rats but decreased plasma insulin by 17% and did not alter plasma NE levels in DIO-prone rats. PVN NE infusions had no effect on plasma epinephrine or glucose or motor activity in either group. Thus reduced PVN alpha 2-adrenoceptor binding is associated with a selective reduction in NE-induced sympathetic activation and insulin release, suggesting a postsynaptic, noradrenergic deficit in DIO-prone rats.

Adrenergic alpha-Agonists↗

PubMed1996

Role of the brain in energy balance and obesity.

Energy balance and body weight are regulated in short, intermediate, and long cycles that are superimposed on each other. We propose that the brain is the primary center of this regulation. The brain has evolved mechanisms for sensing the energy status of the body using neural and metabolic signals such as glucose, insulin, and leptin. It has central processing and storage capacity for handling this afferent information and can change both structurally and functionally in response to its internal and external milieu. The brain regulates energy balance through its control of energy intake on the one hand and expenditure and storage on the other using neurohumoral mechanisms that include the autonomic nervous system. Work in animal models suggests that the brain of obese individuals largely ignores signals of excess adiposity from the periphery, keeping the body weight set point at pathologically high levels. Disordered regulation of neuropeptide Y and monoamine metabolism within the ventromedial hypothalamus is a consistent finding in the brains of obesity-prone and obese rodents. Such dysregulation causes inappropriate neurohumoral control of metabolism and autonomic output to organs such as the pancreas, resulting in increased metabolic efficiency and persistent adiposity. The high recidivism rate in the treatment of obesity suggests that central dysfunction may be due to long-term reorganization of the nervous system in such a way as to perpetuate the abnormally high set point of body weight.

Animals↗

PubMed1995

Lateralized effect of unilateral somatosensory cortex contusion on behavior and cortical reorganization.

Previous studies have shown that rats recover function after unilateral somatosensory cortex lesions, possibly by transfer of information processing to other brain areas not normally involved in those functions. In the present study, adult rats underwent unilateral contusions of the somatosensory cortex with ablation of the barrel receptor field. Behavioral testing with modified beam-walking and sensory neglect tasks demonstrated persistent somatosensory deficits in rats with left contusions but no apparent deficits in right injured animals. After 2 months, the [14C]2-deoxyglucose (2-DG) method was used to show the metabolic activity produced by unilateral stimulation of the facial vibrissae. In left injured animals, cortical metabolic activity rostral and caudal to the injury site was depressed both under basal conditions and during right vibrissal stimulation. On the other hand, comparison of the pattern of [14C]2-DG uptake in the intact, right cortex revealed changes in the pattern of glucose utilization associated with left injury combined with right vibrissal stimulation. Pattern changes were quantified by measuring the area in which glucose utilization was within the highest 25% of this range (high activity area; HAA). Right vibrissal stimulation in left injured rats caused an expansion of this HAA in the intact occipital/temporal cortex. Also, in the intact somatosensory cortex of left injured rats, there was an enlarged HAA whether or not vibrissal stimulation was performed. Thus, a combination of depressed peri-injury metabolic activity and aberrant activity in remote brain areas occurs following unilateral somatosensory cortex injury. It remains to be shown whether these factors ameliorate or contribute to persistent behavioral deficits.

Animals↗

PubMed1995

Widespread and lateralization effects of acute traumatic brain injury on norepinephrine turnover in the rat brain.

Norepinephrine (NE) has been implicated in recovery of function following traumatic brain injury (TBI). While bilateral decrease in brain NE turnover occur at 6-24 h after TBI, it is unknown what effects unilateral TBI might have on brain NE turnover the first few minutes after injury. Her male Sprague-Dawley rats had unilateral confusions of either the right or left somatosensory cortex produced by an air between piston. At 30 min after TBI, brain NE turnover was assessed by measuring the ratio of 3-methoxy-4 hydroxyphenylglycol (MHPG) to NE levels in various brain regions. Both right and left TBI produced 32-103% increases in NE turnover at the injury site and in the ipsilateral cerebral cortex surrounding, rostral and caudal to the injury as compared to the contralateral, uninjured site or to the homologous sites in uninjured controls. NE turnover was also altered selectively in some brain areas not affected by right TBI. Left TBI decreased NE turnover by 29% in the frontal cortex contralateral to the injury and by 24% bilaterally in the hypothalamus while increasing locus coeruleus NE turnover by 72% compared to uninjured controls. Thus, unilateral cortical TBI produced predominantly ipsilateral increases in cortical NE turnover but variable, bilateral changes in NE turnover in subcortical areas which were dependent upon the side of injury. These subcortical differences may explain some of the lateralized effects of cortical injury on post-injury behavior.

Animals↗

PubMed1995

Psychiatric symptoms, atypical dementia, and left visual field inattention in corticobasal ganglionic degeneration.

We longitudinally examined the neuropsychological and psychiatric characteristics of an adult male with pathologically confirmed corticobasal ganglionic degeneration (CBGD). The patient was seen on an inpatient and outpatient basis by members of the Departments of Neurology and Radiology of the University of Miami School of Medicine. Longitudinal neuropsychological testing revealed a lateralized cortical-subcortical dementia and left visual field inattention consistent with neurological and postmortem neuropathological findings of greater right hemisphere dysfunction. Symptoms of depression and obsessive-compulsive symptomatology were also documented. Our findings are consistent with prior reports indicating that CBGD is characterized by lateralized cerebral dysfunction and suggest that a detailed neuropsychological examination is a useful procedure to assist in the differential diagnosis of this movement disorder.

Aged↗

PubMed1995

Reduced norepinephrine turnover in organs and brains of obesity-prone rats.

One-half of the adult male Sprague-Dawley rats fed a diet relatively high in fat, sucrose, and energy content (HE diet) develop diet-induced obesity (DIO). The rest are diet resistant (DR). The role of peripheral and central norepinephrine (NE) activity in predisposing them to these weight gain patterns was assessed before HE diet exposure. Chow-fed male 3-mo-old Sprague-Dawley rats were separated as being prone to become DIO or DR by their high (3.06 +/- 0.14 micrograms) vs. low (1.17 +/- 0.10 micrograms; P = 0.001) 24-h urine NE output, respectively. Turnover of NE, an index of sympathetic activity, was assessed by synthesis inhibition with alpha-methyl-p-tyrosine. DIO-prone rats had significant 53 and 18% reductions in heart and pancreas NE turnover, with interscapular brown adipose tissue turnover comparable to that of DR-prone rats. Hypothalamic NE turnover was significantly decreased by 85 and 60% in the ventromedial nucleus and lateral area vs. DR-prone rats. Although present in DR-prone rats, no turnover was found in the dorsomedial nucleus of DIO-prone rats. Endogenous NE was reduced by 28% in the paraventricular nucleus, whereas arcuate/median eminence turnover was increased by 100% in DIO-prone rats. Amygdalar NE turnover was similar between phenotypes. These intrinsic differences in NE metabolism may play an important role in the development of DIO on HE diets.

Adipose Tissue, Brown↗

PubMed1995

Effects of unbalanced diets on cerebral glucose metabolism in the adult rat.

We measured regional cerebral metabolic rates for glucose and selected cerebral metabolites in rats fed one of the following diets for 6 to 7 weeks: (1) regular laboratory chow; (2) high-fat, carbohydrate-free ketogenic diet deriving 10% of its caloric value from proteins and 90% from fat; and (3) high-carbohydrate diet deriving 10% of its caloric value from proteins, 78% from carbohydrates, and 12% from fat. In preliminary experiments, we found that moderate ketosis could not be achieved by diets deriving less than about 90% of their caloric value from fat. Rats maintained on the ketogenic diet had moderately elevated blood beta-hydroxybutyrate (O.4 mM) and acetoacetate (0.2 mM), and a five- to 10-fold increase in their cerebral beta-hydroxybutyrate level. Cerebral levels of glucose, glycogen, lactate, and citrate were similar in all groups. 2-Deoxyglucose studies showed that the ketogenic diet did not significantly alter regional brain glucose utilization. However, rats maintained on the high-carbohydrate diet had a marked decrease in their brain glucose utilization and increased cerebral concentrations of glucose 6-phosphate. These findings indicate that long-term moderate ketonemia does not significantly alter brain glucose phosphorylation. However, even marginal protein dietary deficiency, when coupled with a carbohydrate-rich diet, depresses cerebral glucose utilization to a degree often seen in metabolic encephalopathies. Our results support the clinical contention that protein dietary deficiency coupled with increased carbohydrate intake can lead to CNS dysfunction.

3-Hydroxybutyric Acid↗

PubMed1995

Early cognitive changes and nondementing behavioral abnormalities in Parkinson's disease.

Early cognitive changes in patients with PD are often subtle and influenced by factors that interact with the disease process, including age and age of disease onset, medication, and the specific constellation of motor symptoms. These factors notwithstanding, there is ample evidence that specific cognitive changes occur early in the course of PD. Whereas language processing deficits are infrequent, subtle changes in olfaction and contrast sensitivity have been repeatedly observed. Executive function deficits are often prominent and, as an integral part of many tasks, also influence performance on a wide range of cognitive measures. This is particularly true for memory and visuospatial dysfunction, two areas that rely heavily on executive demands. Finally, depressive symptoms are also frequent in the early stages of the disease. The significance of early behavioral changes and their prognostic implications are largely unknown and need to be assessed prospectively.

Age of Onset↗

PubMed1994

Increased potency and binding of mazindol to putative brain anorectic receptors in obesity-prone rats.

A class of sodium-sensitive, low affinity binding sites in the brain recognizes [3H]mazindol (MAZ). Competition for [3H]MAZ binding at these sites correlates with the anorectic potency of various phenethylamine drugs suggesting that these might be anorectic binding sites. Here [3H]MAZ binding, in the absence of sodium, was assessed by quantitative receptor autoradiography in rat brain. Binding was saturable, widespread and heterogenous with Kd = 3-229 microM and Bmax = 0.64-21.9 nmol/mg protein in various brain areas. By saturation studies, highest binding was in the somatosensory cortex, central amygdalar nucleus and bed nucleus of the stria terminalis. Hypothalamic subnuclei had intermediate and the piriform cortex had low binding. Rats were identified as prone to develop (DIO-prone) or resist (DR-prone) diet-induced obesity by their low vs. high 24 h urine norepinephrine excretion, respectively. While similar in body weight and basal 30 min intake of 4% sucrose, DIO-prone rats had 28% greater inhibition of sucrose intake by 3 mg/kg MAZ, i.p. (86 +/- 5%) than DR-prone rats (67 +/- 6%; P = 0.05). DIO-prone rats also had 23-55% higher levels of 10 nM [3H]MAZ binding in various hypothalamic and amygdalar nuclei, the somatosensory, piriform and gustatory cortices and thalamus. Given their greater sensitivity the highest dose of MAZ used and their higher binding of MAZ to putative brain anorectic receptors, DIO-prone rats might have a deficiency of an endogenous satiety factor which could predispose them to develop obesity when challenged with high energy, high sucrose diets.

Amygdala↗

PubMed1994

Focal traumatic brain injury causes widespread reductions in rat brain norepinephrine turnover from 6 to 24 h.

The effect of right sensorimotor traumatic brain injury (TBI) in male Sprague-Dawley rats on brain norepinephrine (NE) turnover was assessed by measuring the decline of endogenous NE levels following tyrosine hydroxylase inhibition produced with alpha-methyl-p-tyrosine. Right sensorimotor cortex contusions were produced by a pneumatically driven piston which depressed the dural surface by 2 mm at 3.2 m/s. TBI rats were compared to uninjured, anesthetized controls at 6 h and 24 h after surgery. While NE turnover was not affected at the lesion site at 6 h after TBI, it was either abolished or decreased by 33-75% bilaterally in the hypothalamus and in the cerebral cortex surrounding and rostral to the lesion site. In the cortex caudal to the lesion site, NE turnover was completely abolished. NE turnover in cerebral cortex opposite the lesion site and in the contralateral cerebellum was decreased by 51 and 43%, respectively, at 6 h. At 24 h, NE turnover was either abolished or decreased bilaterally by 45-92% in all cortical areas, in the hypothalamus, cerebellum, locus coeruleus and medulla. Thus, right sensorimotor cortex contusion causes a marked, early and widespread depression of brain NE turnover. Since amphetamine increases NE turnover, this may explain the dramatic improvement in behavioral deficits which occurs following amphetamine administration at 24 h after such lesions.

Animals↗

PubMed1994

A longitudinal examination of crossed aphasia.

OBJECTIVE: To longitudinally examine neuropsychological performance in an adult dextral man with crossed aphasia after cerebrovascular accident. DESIGN: Case report using longitudinal neuropsychological, neurological, and radiological examinations performed in close temporal proximity to one another. SETTING: The patient was seen on both an inpatient and an outpatient basis by members of the Department of Neurology and Radiology of the University of Miami (Fla) School of Medicine. PATIENT: Thirty-four-year-old right-handed monolingual Hispanic man without family history of left-handedness. RESULTS: Initial neuropsychological testing revealed classic Broca's dysphasia, visual neglect, and visuospatial disturbances. The visuospatial disturbance resolved within 6 months whereas expressive language remained severely impaired. There was a dissociation between praxis and language. Mood was jovial with indifference toward his neurologic and cognitive limitations. Serial magnetic resonance imaging studies unequivocally localized the lesions to the right hemisphere, involving the right frontal, anterior parietal, and subcortical white matter. CONCLUSIONS: The clinicoanatomic correlation is compatible with the view that crossed aphasia is a "mirror" representation of that seen in cases of uncrossed aphasia. The course of recovery suggests complete lateralization of language to the right hemisphere with bilateral or crossed representation of nonverbal skills.

Adult↗

PubMed1994

Plasticity of brain alpha-adrenoceptors during the development of diet-induced obesity in the rat.

Male Sprague-Dawley rats, which are prone to develop diet-induced obesity (DIO) on a high energy (HE) diet can be separated from rats which are diet-resistant (DR) by several prospective tests. Using such tests, chow-fed DRl-prone rats have higher binding of 3H paraminoclonidine (PAC) to brain alpha2-adrenoceptors than do DIO-prone rats. These differences disappear after 3 months on a HE diet. To study the predictive value of these tests and possible associated changes in presynaptic membrane composition, brain alpha3(1-) (1nM 3H prazosin) and (alpha2-adrenoceptor (1nM) 3-H PAC) binding and synaptosomal fatty acid composition were assessed in 3-month-old male rats separated by weight gain into DR and DIO groups after 1 month on a HE diet. DIO had comparable total caloric intake but gained 30% and 43% more weight and were hyperinsulinemic compared to DR and chow-fed rats, respectively. After 1 month on a HE diet, DR rats still had 15%-53% higher 3H PAC binding than DIO and/or chow-fed rats in 14 of 16 brain areas assessed. A phenotype effect was present primarily in the amygdala where DR rats had higher 3H PAC binding than DIO rats. A diet effect was seen in some hypothalamic nuclei where both DR and DIO rats had higher 3H PAC binding than chow-fed rats. Conversely, DIO rats had 14%-21% higher 3H prazosin binding than DR rats in 3 brain areas. Changes in brain synaptosomal membranes' fatty acids reflected both phenotype and diet effects. Thus, while diet composition affects presynaptic membrane composition and alpha2-adrenoceptor binding in both DR and DIO rats, the predominance of plasticity of these parameters is limited to the brains of DR rats. This suggests that such plasticity may be an important determinant of the ability to resist the development of diet-induced obesity on a HE diet.

Adrenergic alpha-Agonists↗